Ses 5 ANS and Hypertension CVS Flashcards
(21 cards)
detail the neurotransmitters and receptors involved in the
autonomic nervous system
Preganglionic neurones of both divisions release Ach which acts on nicotine Ach receptors on postganglionic cell.
In sympathetic post ganglionic - usually releases noradrenaline which binds to adrenergic receptors.
In para post ganglion Ach released but binds to muscarinic ACh receptors.
ANS what does it control notion for examples
– smooth muscle (vascular and visceral)
– exocrine secretion
– rate and force of contraction in the heart
Adrenoreceptors and muscarinic receptors
A = G protein-coupled receptors
• α-adrenoreceptors
– α1-(Gq), α2-(Gi)
• β-adrenoreceptors (Gs)
– β1, β2, also β3
M = G protein-coupled receptors
M1(Gq), M2(Gi), M3(Gq)
Both
• Different tissues can have different subtypes
– Allows for diversity of action
– Selectivity of drug action
ANS control of heart rate and force of contraction - nerve, where does it act, receptors
Para input to heart:
10th cranial nerve - vagus
Synapse with postganglionic cells on epicardial surface or within
walls of heart predominantly at SA and AV node.
Acts on M2-receptors:
Dec HR/ -ve chronotropic effect
Dec AV node conduction velocity
Sympa
Innervate SA node, AV node and myocardium - release NA
β1 adrenoreceptors
Inc HR and force of contraction (+ve inotropic effect)
explain the cellular mechanisms by which the ANS controls heart rate
Sympa
G-protein coupled receptors (Gs which stimulates adenylate cyclase) - beta 1
Increase cAMP which inc speeds up funny current which speeds up pacemaker potential
Para
G-protein coupled receptors (Gi which inhibits adenylate cyclase)
Increase K+ conductance (dec depolarisation) and decrease cAMP
explain the cellular mechanisms by which the ANS controls force of contraction in the heart
noradrenaline increase force of contraction
NA acting on β1 receptors in
myocardium causes an increase
in cAMP → activates PKA
- Phosphorylation of Ca2+ channels increases Ca2+ entry during the plateau of the AP
- Increased uptake of Ca2+ in
sarcoplasmic reticulum
• More Ca2+ available for release from stores
Leads to increased force of
contraction
describe the mechanisms which control contraction of vascular
smooth muscle cells
Had basal vasomotor tone
most vessels receive sympathetic innervation - mostly α1-adrenoreceptors - NA from SNS - vasoconstriction.
Stimulates IP3 production
Calcium-calmodulin complex activates MLCK which phosphorylates the regulatory myosin light chain
Plus DAG inhibiting myosin light chain phosphatase
Increase in [Ca2+]intracellular from stores and influx of extracellular Ca2+ → contraction of smooth muscle
Gq coupled - leads to inositol trisphosphate (IP3) and
diacyl glycerol (DAG) production
At high levels adrenaline binds to alpha 1
coronary and skeletal muscle vasculature also have β2-receptors - adrenaline has a higher affinity for them at normal levels - causes vasodilation- Increases cAMP → PKA → opens potassium channels + inhibits MLCK→ relaxation of smooth muscle
Gs coupled
Role of local metabolites in vsm
Active tissue produces more metabolites
Local increases in metabolites have a strong vasodilator effect
ensuring adequate perfusion of skeletal and coronary muscle
explain the role of the autonomic nervous system in controlling
peripheral resistance
Inhibition of SNS to heart and vessels Activation of PNS to heart in response to increase arterial BP
describe the baroreceptor reflex
Nerve endings in the carotid sinus and aortic arch are sensitive to stretch.
Increased arterial pressure stretches these receptors.
Message sent to medulla
Neg effect on SNS - bradycardia and vasodilation to lower BP
The baroreceptor reflex is important for maintaining arterial BP over short term.
HOWEVER Baroreceptors can re-set to higher levels with persistent increases in blood
pressure.
define the stages of hypertension
Stage 1 hypertension ≥ 140/90 mmHg
Stage 2 hypertension ≥160/100 mmHg
Severe hypertension ≥ 180 systolic or ≥ 110 diastolic
explain the impact of hypertension on organs and tissues in the body
Damaging effects on heart and vasculature
Potentially leading to heart failure, MI, stroke, renal failure and retinopathy
Brain, eyes, heart, kidneys, arteries
Medium and longer term control of blood pressure
What is main part of their response
4
Directed at controlling sodium balance and thus extracellular fluid volume
- Renin-angiotensin-aldosterone system
- Sympathetic nervous system 3. Antidiuretic hormone (ADH)
- Atrial natriuretic peptide (ANP)
RAAS
Reduced NaCl delivery to macula dense of distal tubule
Reduced perfusion pressure in the kidney causes the release
of renin detected by baroreceptors in afferent arteriole
Sympathetic stimulation to juxtaglomerular apparatus to inc renin
Converts angiotensinogen to angiotensin I
ACE(angiotensin converting enzyme - also breaks down bradykinin which is a vasodilator) converts it to angiotensin II
This causes vasoconstriction, stimulates Na+ absorption in kidneys, stimulates aldosterone, inc ADH release. Main actions via AT1 receptor.
aldosterone:
• acts on principal cells of collecting ducts
• stimulates Na+ and therefore water reabsorption
• activates apical Na+ channel (ENaC, Epithelial Na Channel)
and apical K+ channel
• also increases basolateral Na+ extrusion via Na/K/ATPase
ACE inhibitors used to stop this process and has hypotensive effects.
Sympathetic nervous system
reduce renal blood flow
– Vasoconstriction of arterioles
– Decrease GFR – decrease Na+ excretion
• Activates apical Na/H-exchanger and basolateral Na/K
ATPase in PCT
• Stimulates renin release from JG cells
Antidiuretic Hormone (ADH)
Increases water reabsorption in distal nephron (AQP2)
stimulates Na+ reabsorption
– Acts on thick ascending limb
– stimulates apical Na/K/Cl co-transporter
Causes vasoconstriction
Natriuretic peptides
promotes Na+ excretion along nephron - Causes natriuresis (loss of sodium into urine)
• synthesised and stored in atrial myocytes
• released from atrial cells in response to stretch
– reduced filling of the heart – less stretch – less ANP released
Causes vasodilation of the afferent arteriole - Increased blood flow increases GFR
2 other molecules that involve in BP
Prostaglandins - Locally acting prostaglandins (mainly PGE2) enhance glomerular filtration and reduce Na+ reabsorption
Dopamine - reduces reabsorption of NaCl
– Inhibits NH exchanger and Na/K ATPase in principal cells of PCT
Secondary hypertension adrenal
Conn’s syndrome – aldosterone secreting adenoma - hypertension and hypokalaemia
• Cushing’s syndrome – excess secretion of glucocorticoid cortisol – at high concentration acts on aldosterone receptors
• Tumour of the adrenal medulla – phaeochromocytoma – secretes catecholamines
Secondary hypertension: Renovascular disease
Occlusion of the renal artery (renal artery stenosis) causes a fall in perfusion pressure in that kidney
• Decreased perfusion pressure leads to increased renin production
Treating hypertension notion
First = lifestyle
Eg exercise, diet, less salt and alcohol
Meds
Raas
ACE inhibitors eg captopril
Angiotensin Receptor Blockers (ARBs) eg Losartan
Vasodilators
L-type Ca channel blockers (eg Verapamil) – reduce Ca2+ entry to vascular smooth muscle cells
α1 receptor blockers (eg Doxazosin) - can cause postural hypotension
Diuretics
Beta blockers - reduce SNS - used when previous MI
